Project Abstract: Parkinson's disease (PD) is one of the most common neurological disorders, and the Veterans Health Administration treats approximately 40,000 veterans with PD each year nationwide. PD has traditionally been considered a motor disorder, but it is now clear that there are cognitive symptoms as well, with at least 60% of non-demented patients impaired in one or more cognitive domains. While cognitive function is fundamental to normal motor behavior, the development of treatment has focused primarily on motor symptoms. There is growing evidence in the field of cognitive rehabilitation that training strategies focused on specific aspects of cognition can improve treatment outcomes in neurological disorders. However, there is no model of cognitive impairment that allocates specific neuropsychological rehabilitation strategies to cognitive dysfunction. In addition, there has been no systematic evaluation of the efficacy of cognitive rehabilitation in PD subjects, and the neural mechanisms underlying cognitive rehabilitation in PD are unknown. We have three aims, 1) to systematically evaluate cognitive rehabilitation in PD subjects, 2) to examine the neural mechanisms underlying cognitive rehabilitation in PD and 3) to assess the ecological validity of cognitive rehabilitation in PD. We will focus on a single aspect of cognitive function, the decision to initiate a movement. Movements can be internally generated or externally cued, and motor deficits in PD are typically linked to internally generated (IG) movements. Our approach is to use PC-based adaptive training to improve performance of IG movement initiation in patients with PD. The protocol is designed to drive beneficial neuroplastic changes using paradigms similar to those that have shown promising results in traumatic brain injury patients. In addition, we will use fMRI to measure activity in underlying BG-thalamocortical circuits, specifically patterns of insufficient normal activation and recruitment of additional brain areas, and measure changes in these patterns related to training. Finally, because the goal of any research regarding the pathophysiology of disease is to improve the lives of patients with the disease, behavioral and neuropsychological measures will be correlated with fMRI measured functional abnormalities before and after training. Improvement in the initiation of internally generated movements has the potential to dramatically improve daily functioning including reducing falls, improving language production and increasing proficiency of daily self initiated tasks such as opening a medication bottle or preparing a meal. Efforts to provide new and better treatment approaches for PD are crucial to the mission of the Veterans Health Administration. The key contribution of this work is that we will provide a novel adjunct therapy in the treatment of the cognitive symptoms of PD that is non-invasive, free from side effects, cost effective, and easily implemented. PUBLIC HEALTH RELEVANCE: Narrative Parkinson's disease (PD) is one of the most common neurological disorders. Most people think of PD as a disease that causes problems with movement, such a tremor or difficulty walking, however, it is now clear that PD also involves problems with cognition, or thinking, as well as movement. These thought disorders, such as planning a movement, are an important part of movement problems in PD, but little research has been done to understand the effects of PD on thinking, and treatment still focuses for the most part on movement. We will test the effectiveness of cognitive rehabilitation in PD patients and use brain imaging to measure changes in brain function related to training. We will also measure how well training helps people with PD to perform activities of daily living. The key contribution of this work is that we will provide a new therapy in the treatment of the cognitive symptoms of PD that is non-invasive, free from side effects, cost effective, and easily implemented.